By CHARLOTTE HSU

“HAMLET has the potential minimize the concentrations of antibiotics we need to use to fight infections, and enable us to use well-established antibiotics against resistant strains again.”

Anders Hakansson, Assistant Professor

Department of Microbiology and Immunology

A protein complex found in human breast milk can help reverse
the antibiotic resistance of bacterial species that cause dangerous
pneumonia and staph infections, according to new UB research.

In petri dish and animal experiments, the protein
complex—called Human Alpha-lactalbumin Made Lethal to Tumor
Cells (HAMLET)—increased bacteria’s sensitivity to
multiple classes of antibiotics, such as penicillin and
erythromycin.

The effect was so pronounced that bacteria including
penicillin-resistant Streptococcus pneumoniae and
methicillin-resistant Staphylococcus aureus (MRSA) regained
sensitivity to the antibiotics they previously were able to beat,
says researchers Anders Hakansson, Laura Marks and Hazeline
Hakansson, all in UB’s Department of Microbiology and
Immunology.

HAMLET’s effects against S. pneumoniae were published
in the journal PLOS ONE in August 2012 with Marks, Anders
Hakansson and UB PhD student Emily Clementi as authors.
HAMLET’s effects on S. aureus appeared in PLOS ONE on
May 1.

“HAMLET has the potential minimize the concentrations of
antibiotics we need to use to fight infections, and enable us to
use well-established antibiotics against resistant strains
again,” says Anders Hakansson, lead researcher and UB
assistant professor of microbiology and immunology who has long
been interested in the protective effect of breast-feeding against
infections.

The findings hold great promise in an era when hospitals are
struggling to contain drug-resistant “superbugs” like
MRSA, the culprit behind lethal hospital-acquired staph
infections.

Bacteria seem to have difficulty developing resistance to
HAMLET, dying in huge numbers even after being exposed to HAMLET
for many generations.

Marks, an MD/PhD student in the School of Medicine and
Biomedical Sciences’ Medical Scientist Training Program,
described another of HAMLET’s benefits: “Unlike
synthetic drugs, HAMLET is a naturally occurring human milk
protein-lipid complex, and so is not associated with the types of
toxic side effects that we so frequently see with the high-powered
antibiotics needed to kill drug-resistant organisms.”

The idea to test HAMLET in combination with other antibiotics
was inspired, in part, by a presentation Marks saw on using drug
cocktails to treat HIV.

“What really hit home for me in this lecture was the idea
of using drug combinations where each drug had a different
mechanism that could enhance the action of the other drug as an
appealing way to optimize therapy for resistant organisms,”
she says. “I was immediately curious to see if using HAMLET
together with existing therapies could result in synergistic
interactions.”

UB’s Office of Science, Technology Transfer and Economic
Outreach (STOR) has filed a provisional patent application
detailing HAMLET’s antibiotic capabilities, and Anders and
Hazeline Hakansson have founded a company called Evincor to further
develop HAMLET.

“The pharmaceutical industry is currently reluctant to
develop antibiotics because they are only used for a short time and
they will be used infrequently initially and only when nothing else
works,” Hazeline Hakansson says. “HAMLET, on the other
hand, is more of an adjuvant and can be used widely in combination
with common antibiotics; it already has a huge potential market
that is only going to increase the next couple of years as
antibiotic resistance increases.

“Some people estimate that it’s only a question of
time before we run out of antibiotics to combat bacteria,”
she continues. “HAMLET is promising because we haven’t
been able to make bacteria resistant to it and it kills bacteria
via a mechanism that is clearly different from that of commonly
prescribed antibiotics.”

The Hakanssons, a husband-and-wife team, say the next step is to
test HAMLET on additional strains of S. pneumoniae and S.
aureus—including those currently infecting
patients—and to expand the in-vivo infection models used for
testing to provide a proof of principle.

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